Cell membranes are primarily transducers by which extracellular signals are transmitted to the interior of the cell. In other instances, however, intracellular events can effect the interactions of the cell with its extracellular environment. The primarily pathophysiologic event in sickle cell disease, polymerization of hemoglobin S within sickle red blood cells (RBCs), leads to alterations in sickle RBC membranes that enhance interactions between sickle RBCs and other blood cells, including vascular endothelial cells and monocytes/macrophages. In investigating the molecular mechanisms that mediate these interactions, our laboratory has made the novel observation that significant numbers of cell-cell conjugates involving sickle RBCs and T lymphocytes are found in the blood of patients with homozygous (SS) sickle cell disease. These conjugates could participate in the pathophysiologic sequences leading to hemolysis and vaso-occlusive crisis, the two major clinical problems in sickle cell disease. The objectives of this project are to use time-resolved laser and video microscopy techniques to investigate the molecular mechanisms that mediate adhesion of sickle RBCs to T lymphocytes, including the role of binding interactions between CD2 on the lymphocyte surface and CD58 (LFA- 3) on the RBC surface, and the mechanisms by which sickle RBC membranes and T lymphocyte membranes are altered to enhance lymphocyte-RBC conjugate formation